Granzyme B PET/CT, Immune Checkpoint Inhibitor, Triple Negative Breast Cancer
Conditions
Brief summary
This study plans to enroll 30 patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who are scheduled to receive at least two cycles of a regimen containing an immune checkpoint inhibitor (ICI). All ICI treatments must be administered in accordance with current clinical indications. For patients who intend to participate in a clinical trial involving an ICI, they must meet the eligibility criteria of that specific trial protocol. After screening and enrollment, participants will undergo a \[68Ga\]Ga-DOTA-GSI PET/CT (Granzyme B PET/CT) scan before initiating the ICI-containing regimen and again after Cycle 2 (C2). Participants will continue the ICI regimen until disease progression, with tissue biopsies performed as needed. By integrating patients' baseline clinical characteristics, treatment outcomes, and prognostic information, this study aims to conduct a comprehensive analysis. The objective is to investigate whether the following factors, as assessed by Granzyme B PET/CT, can serve as early predictors of response to immunotherapy in patients with advanced breast cancer: baseline Granzyme B expression levels, immunotherapy-activated Granzyme B levels after C2, and the heterogeneity of Granzyme B expression at baseline and after C2.
Interventions
OTHER[68Ga]Ga-DOTA-GSI PET/CT (Granzyme B PET/CT)
Granzyme B is a highly specific cytotoxic molecule. By binding to Granzyme B, Granzyme B-PET can visualize the distribution and activity of this enzyme within the tumor microenvironment on PET images. Performing Granzyme B-PET scans before and after immunotherapy allows for the monitoring of changes in active intratumoral immune cells during treatment. This, in turn, helps to assess whether the therapy has effectively activated the immune system and the extent of tumor cell killing. Granzyme B-PET images provide a measure of intratumoral Granzyme B uptake, thereby enabling an objective evaluation of the cytotoxic capacity of immune cells.
Sponsors
Fudan University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Histologically confirmed unresectable locally advanced or metastatic breast cancer, with immunohistochemistry (IHC) results indicating negativity for ER, PR, and Her-2. If pathology from a metastatic lesion is available, its histology will take precedence. ER and PR negativity is defined as: ER \<1% positive and PR \<1% positive, OR ER \<10% with weak positivity and PR \<10% with weak positivity. Her-2 negativity is defined as: an IHC score of 0 or 1+; or an IHC score of 2+ with a negative FISH test result. For patients with an IHC score of 0 or 1+, a FISH test is optional but must be negative if performed. 3. Decision by the clinician to treat with a regimen containing an immune checkpoint inhibitor (ICI), with the patient scheduled to receive at least 2 cycles of treatment. 3.1. If the patient intends to participate in an ongoing clinical trial involving an ICI at our department, they must meet the inclusion and
Exclusion criteria
of that specific trial. ICIs involved in clinical trials at our department include, but are not limited to, Pembrolizumab, Sintilimab, Toripalimab, and QL1706. 3.2. For patients not enrolled in a clinical trial, they must have PD-L1 positive status (CPS ≥ 1), and the intended drug must be Toripalimab, as approved by the National Medical Products Administration (NMPA). 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Evidence of radiological or objective disease progression during or after the most recent systemic therapy prior to study entry, or intolerance to the toxicity of prior treatment. 6. Life expectancy of ≥ 12 weeks at the time of screening. 7. Presence of at least one measurable lesion that has not been previously irradiated. The lesion must have a longest diameter of ≥10 mm at baseline as measured by CT or MRI (for lymph nodes, the short axis must be ≥15 mm). In cases where only bone lesions are present, lytic or mixed lytic-blastic bone lesions that can be assessed by CT, MRI, or X-ray are acceptable. 8. Left Ventricular Ejection Fraction (LVEF) ≥ 50% within 28 days prior to randomization. 9. Adequate organ and bone marrow function within 14 days prior to randomization. The most recently obtained results for all parameters listed below must be used to meet the eligibility criteria: 1. Hemoglobin ≥ 9 g/dL 2. Absolute Neutrophil Count (ANC) ≥ 1,500/mm³ 3. Platelet count ≥ 100,000/mm³ 4. At baseline, Total Bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) if no liver metastases are present, or \< 3 × ULN for patients with Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases. 5. ALT and AST ≤ 3 × ULN, or \< 5 × ULN for patients with liver metastases. 6. Serum albumin ≥ 2.5 g/dL 7. Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula). 8. International Normalized Ratio (INR) or Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) or activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN. 10. From the screening period through the entire study treatment period and for 7 months after the last dose of study treatment, female patients must not donate or retrieve oocytes (eggs) for personal use. Breastfeeding must be avoided during this period. If oocyte preservation is desired, it should be completed prior to randomization in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive Predictive Value (PPV) | Up to disease progression, an average of 1 year | Positive Predictive Value of Granzyme B Expression as Assessed by Granzyme B PET/CT for Objective Response. |
Countries
China
Contacts
CONTACTJuan Jin, Attending physician
Outcome results
None listed